Design And Optimization Of Nucleic Acid Delivery Systems For Clinical Applications: A Review

Abstract

Recent advances in nucleic acid science have significantly expanded the scope of precision medicine, enabling therapeutic strategies that extend beyond conventional small molecules and biologics. This review examines the development and current state of mRNA- and nucleic acid based delivery platforms, emphasizing their growing importance in next-generation therapeutics. We begin with a brief historical overview, describing early challenges related to molecular instability, inefficient targeting, and limited cellular uptake, and how progressive technological innovations have successfully addressed these limitations. The mechanisms underlying mRNA and nucleic acid drug delivery are then discussed, with particular focus on their ability to regulate gene expression and modulate immune responses with high specificity. Key delivery technologies are highlighted, including lipid nanoparticles, polymer- based carriers, and conjugate systems, along with recent formulation advances that have improved safety, efficacy, and translational potential. Ongoing challenges such as cargo degradation, unintended immune activation, and suboptimal delivery efficiency are critically evaluated, and practical strategies to overcome these barriers are presented. Basically, the review explores future directions in the field, underscoring the promise of nucleic acid therapeutics in personalized medicine and the importance of continued research to optimize delivery platforms. Overall, this article provides a comprehensive overview of the evolving landscape of nucleic acid-based therapeutics and aims to inform clinicians, researchers, and pharmaceutical scientists about their current applications and future potential in modern healthcare.